When Escitalopram is Surrounded by Ethanol: A DFT and QTAIM Approach to Analyze The Drug and The Alcohol Interactions and It’s Possible Outcomes

Öz

In the scope of this work the antidepressant escitalopram was surrounded by ethanol commonly referred as alcohol step by step and the possible results of this invasion on escitalopram drug molecule were examined principally by density functional theory methods. Also for analyzing hydrogen bonding interactons, quantum theory of atoms in molecules was used. In this method, the nature of interaction is classified whether it is covalent, partially covalent or noncovalent. According to the results it was observed that the escitalopram under attack by ethanol shows quite different chemical properties which must be taken into account when used together with alcohol.

Anahtar Kelimeler

• Escitalopram
• Drug-Alcohol Interaction
• DFT
• QTAIM

Destekleyen Kurum

TUBITAK, Eskişehir Technical University

Proje Numarası

1919B012302888; 24LÖP001

Etik Beyan

In this study, we undertake that all the rules required to be followed within the scope of the "Higher Education Institutions Scientific Research and Publication Ethics Directive" are complied with, and that none of the actions stated under the heading "Actions Against Scientific Research and Publication Ethics" are not carried out.

Teşekkür

Authors acknowledge FenCluster System of Ege University for the calculations. This study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) BİDEB 2209-A Grant No 1919B012302888 and Eskişehir Technical University Scientific Research Projects Commission under grant no 24LÖP001.

Essitalopram Ethanol ile Çevrelendiğinde: İlaç ve Alkolün Etkileşimlerini ve Olası Sonuçlarını Analiz Etmek için QTAIM ve DFT Yaklaşımı

Öz

Bu çalışma kapsamında antidepresan essitalopram, yaygın olarak alkol olarak adlandırılan etanol ile adım adım çevrelendi ve bu çevrelemenin essitalopram ilaç molekülü üzerindeki olası sonuçları yoğunluk fonksiyonel teorisi ile incelendi. Ayrıca hidrojen bağı etkileşimlerini analiz etmek için moleküllerdeki atomların kuantum teorisi kullanılmıştır. Bu yöntemde, etkileşimin doğası kovalent, kısmi kovalent veya kovalent olmayan olarak sınıflandırılır. Elde edilen sonuçlara göre etanol ile çevrelenen essitalopramın, alkolle birlikte kullanıldığında dikkate alınması gereken oldukça farklı kimyasal özellikler gösterdiği gözlemlendi.

Anahtar Kelimeler

• Essitalopram
• İlaç-Alkol Etkileşimi
• DFT
• QTAIM

Destekleyen Kurum

TÜBİTAK, Eskişehir Teknik Üniversitesi

Proje Numarası

1919B012302888; 24LÖP001

Etik Beyan

Bu çalışmada "Yükseköğretim Kurumları Bilimsel Araştırma ve Yayın Etiği Yönergesi" kapsamında uyulması gereken tüm kurallara uyulduğunu, "Bilimsel Araştırma ve Yayın Etiğine Aykırı Eylemler" başlığı altında belirtilen eylemlerden hiçbirinin gerçekleştirilmediğini taahhüt ederiz.

Teşekkür

Yazarlar hesaplamalar için Ege Üniversitesi FenCluster Sistemini kullandıkları için Ege Üniversitesine teşekkür etmektedirler. Bu çalışma, Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK) BİDEB 2209-A 1919B012302888 Hibesi ve 24LÖP001 Hibesi kapsamında Eskişehir Teknik Üniversitesi Bilimsel Araştırma Projeleri Komisyonu tarafından desteklenmiştir.

Kaynakça

1. [1] Peacock A., Leung J., Larney S. 2018. Global Statistics on Alcohol, Tobacco and Illicit Drug Use: 2017 Status Report. Addiction, 113, 1905-1926.
2. [2] Kaufman, E., 1976. The Abuse of Multiple Drugs. I.Definition, Classification, and Extend of Problem. The American Journal of Drug and Alcohol Abuse, 3, 279-292.
3. [3] Singh, A. 2021. Interaction of Alcohol with Drugs of Abuse and Medicines. Neurobiology of Alcohol and Brain. Academic Press, 75-140.
4. [4] Guerzoni, S., Pellesi, L., Pini, L.A., Captuo, F. 2018. Drug-drug interactions in the treatment for alcohol use disorders: A comprehensive review. Pharmacological Research, 133, 65-76.
5. [5] Zheng, P., Wang, Y., Chen, L., Yang, D., Meng, H., Zhou, D., Zhong, J., Lei, Y., Melgiri N.D., Xie, P. 2013. Identification and Validation of Urinary Metabolite Biomarkers for Major Depressive Disorder. Molecular & Cellular Proteomics, 12 (1), 207-214.
6. [6] Chirit, A.L., Gheorman, V., Bondari, D., Rogoveanu, I. 2015. Current Understanding of The Neurobiology of Major Mepressive Disorder. Romanian Journal of Morphology and Embryology, 56(2 Suppl), 651-658.
7. [7] Owens, M.J., Knight, D.L., Nemeroff, C.B. 2001. Second-generation SSRIs:human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biological Psychiatry, 50, 345-350.
8. [8] Jonathan, R.T., Davidson, M.D., Bose A., Korotzer, A., Zheng, H. 2004. Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study. Depression and Anxiety, 19, 234-240.

9. [9] Dhillon, S., Scott, L.J., Plosker, G.L. 2006. Escitalopram A Review of its Use in the Management of Anxiety Disorders. CNS Drugs, 20, 763-790.
10. [10] Omurtag Özgen P.S., Durmaz H., Parlak C., Alver Ö., Bağlayan Ö. 2020. Non-covalent functionalization of single walled carbon nanotubes with pyrene pendant polyester: A DFT supported study. Journal of Molecular Structure, 1209, 127943.
11. [11] Parlak, C., Tepe, M., Bağlayan, Ö., Alver, Ö. 2020 Investigation of detection and adsorption properties of β-propiolactone with silicon and aluminum doped fullerene C60 using density functional theory. Journal of Molecular Structure, 1217, 128346.
12. [12] Parlak, C., Alver, Ö., Bağlayan, Ö. 2021. Quantum mechanical simulation of Molnupiravir drug interaction with Si-doped C60 fullerene. Computational and Theoretical Chemistry, 1202, 113336.
13. [13] Afzal, Q.Q., Rafique, J., Jaffar, K., Perveen, M., Iqbal, J., Al-Buriahi, M.S., Alomairy, S., Alrowaili, Z.A., Somaily, H.H. 2022. DFT study of 2D graphitic carbon nitride based preferential targeted delivery of levosimendan, a cardiovascular drug. Computational and Theoretical Chemistry, 1209, 113584.
14. [14] Ramana, P. V., Sundius, T., Muthu, S., Mouli, K. C., Krishna, Y. R., Prasad, K. V., Devi, R. N., Irfan, A., Santhamma, C., 2022. Spectroscopic, quantum mechanical, electronic excitation properties (Ethanol solvent), DFT investigations and molecular docking analysis of an anti-cancer drug Bendamustine. Journal of Molecular Structure, 1253, 132211.
15. [15] R.F.W. Bader. 1990. Atoms in Molecules: A Quantum Theory, Clarendon, New York.
16. [16] Rozas, I., Alkorta, I., Elguero, J. 2000. Behavior of ylides containing N, O, and C atoms as hydrogen bond acceptors. Journal of the American Chemical Society, 122, 11154–11161.
17. [17] Espinosa, E., Molins, E., Lecomte, C. 1998. Hydrogen bond strengths revealed by topological analyses of experimentally observed electron densities. Chemical Physics Letters, 285, 170–173.
18. [18] Mata, I., Alkorta, I., Espinosa, E., Molins, E. 2011. Relationships between interaction energy, intermolecular distance and electron density properties in hydrogen bonded complexes under external electric fields. Chemical Physics Letters, 507, 185–189.
19. [19] Parlak, C., Alver, Ö., Bağlayan, Ö., Ramasami, P. 2022. Theoretical insights of the drug-drug interaction between favipiravir and ibuprofen: a DFT, QTAIM and drug-likeness investigation. Journal of Biomolecular Structure and Dynamics, 41, 10, 4313–4320.
20. [20] Gutowski, M., Chalasinski, G. 1993. Critical evaluation of some computational ap- proaches to the problem of basis set superposition error, The Journal of Chemical Physics, 98, 5540–5554.
21. [21] Frisch, M. J., Trucks, G. W., Schlegel, H. B. et al. 2016. Gaussian 16, Revision C.01, Gaussian Inc., Wallingford, CT.
22. [22] Dennington, R.D., Keith, T.A., Millam, J.M., 2016. GaussView 6.0.16, Gaussian Inc.
23. [23] Lu, T., Chen, F. 2012. Multiwfn: A multifunctional wavefunction analyser, Journal of Computational Chemistry, 33, 580–592.
24. [24] Suliman, F. O., Al-Nafai, I., Al-Busafi, S. N. 2014. Synthesis, characterization and DFT calculation of 4-fluorophenyl substituted tris(8-hydroxyquinoline)aluminum(III) complexes. Spectrochimica acta. Part A, Molecular and Biomolecular Spectroscopy, 118, 66–72.
25. [25] Frenking, G., Shaik, S. 2014. The chemical bond. Wiley-VCH, Weinheim, Germany.
26. [26] Antony Danish, I., Jebasingh Kores, J., Sasitha, T., Winfred Jebaraj, J. 2021. DFT, NBO, HOMO-LUMO, NCI, stability, Fukui function and hole – Electron analyses of tolcapone. Computational and Theoretical Chemistry, 1202, 113296.